1. Field of the Invention
The present invention relates to treatment of tissues in a living organism, and in particular to moving a support structure or treatment delivery device, or both, to compensate for tissue movement relative to the treatment delivery device caused by biological activity of the organism, such as respiration, during treatment delivery, such a during delivery of a dose of radiation. Embodiments of the invention are also directed to a method and/or device for predicting the position of a target site, such as a tumor, inside a human or other animal body in real time or near real time using surrogates.
2. Description of the Related Art
Tumors in the thoracic and abdominal regions are susceptible to motion during normal respiration. Treating these tumors with, for example, a radiation beam or zone must take into account this moving target. Uncorrected, this leads to at least part of the tumor receiving less than the desired dose while that part is outside the treatment zone. Conventional methods to account for this problem involve the addition of a “treatment margin” so that a greater volume of tissue, including normal healthy tissue, is treated to therapeutic doses. Subjecting normal tissue to therapeutic doses can lead to possible complications.
Studies in the thorax and abdomen have shown that respiration can cause tumors to move up to 2 cm (see, for example, Kitamura K, Shirato H, Seppenwoolde Y, Shimizu T, Kodama Y, Endo H, Onimaru R, Oda M, Fujita K, Shimizu S, Miyasaka K. Tumor location, cirrhosis, and surgical history contribute to tumor movement in the liver, as measured during stereotactic irradiation using a real-time tumor-tracking radiotherapy system. Int J Radiat Oncol Biol Phys. vol. 56, pp 221-228, 2003). Although 3-D conformal and intensity-modulated radiation therapy (IMRT) can potentially deliver highly conformal doses to the tumor while sparing normal healthy tissues, respiration-induced tumor motion can produce under-dosing of the tumor's periphery (see, for example, Bortfeld T, Jokivarski K, Goitein M, Kung J, Jiang S B. Effects of intra-fraction motion on IMRT dose delivery: statistical analysis and simulation. Phys Med Biol vol. 47, pp 2203-2220, 2002; and Naqvi S A, D'Souza W D. A stochastic convolution/superposition method with isocenter sampling to evaluate intrafraction motion effects in IMRT. Med Phys vol. 32, pp 1156-1163, 2004).
Conventional methods to deal with tumor motion have involved allowing an adequate margin when designing the treatment fields or defining the planning tumor volume (PTV). Advanced methods to manage respiratory-induced tumor motion during radiation delivery include breath-holds, both voluntary (see, for example, Rosenzweig K E, Hanley J, Mah D, Mageras G, Hung M, Toner S, Burman C, Ling C C, Mychalczak B, Fuks Z, and Leibel S A. The deep inspiration breath-hold technique in the treatment of inoperable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys vol. 48, pp 81-87, 2000) and forced (see, for example, Dawson L A, Brock K K, Kazanjian S, Fitch D, McGinn C J, Lawrence T S, Ten Haken R K, Balter J. The reproducibility of organ position using active breathing control (ABC) during liver radiotherapy. Int J Radiat Oncol Biol Phys vol. 51, pp 1410-1421, 2001), beam gating (see, for example, Shirato H, Shimizu S, Kunieda T, Kitamura K, van Herk M, Kagei K, Nishioka T, Hashimota S, Fujita K, Aoyama H, Tsuchiya K, Kudo K, and Miyasaka K. Physical aspects of a real-time tumor-tracking system for gated radiotherapy. Int J Radiat Oncol Biol Phys vol. 48, pp 1187-1195, 2000) and real-time tumor tracking. Tumor-tracking using conventional linear accelerators for beam delivery is conventionally based on moving a multi-leaf collimator (MLC). (See for example, Keall P J, Kini V R, Vedam S S, and Mohan R. Motion adaptive x-ray therapy: a feasibility study. Phys Med Biol vol. 46, pp 1-10, 2001, the entire contents of which are herby incorporated by reference as if fully set forth herein). Tracking using repositioning of the linear accelerator has also been described (Adler J R, Murphy M J, Chang S D. Image-guided robotic radiosurgery. Neurosurgery vol. 44, pp 1299-1307, 1999; Schweikard A, Glosser G, Boddulura M, Murphy M J, and Adler J R. Robotic motion compensation for respiratory movement during radiosurgery. Comput Aided Surg vol. 5, pp 263-277, 2000; Ozhasoglu C and Murphy M J. Issues in respiratory motion compensation during external-beam radiotherapy. Int J Radiat Oncol Biol Phys vol. 52, pp 1389-1399, 2002, the entire contents of each of which are herby incorporated by reference as if fully set forth herein). A CYBERKNIFE™ from Accuray Inc. of Sunnyvale, Calif., uses a miniaturized linear accelerator mounted on an industrial robot.
Methods for managing respiration-induced motion while a fraction of the radiation dose (or other treatment) is delivered (called herein “intra-fraction” motion) may be broadly grouped into breath-hold methods, gating methods and real-time tracking methods. Breath-hold and gating techniques pose the disadvantage of increased treatment time. The duty cycle for gating is typically 25% on and 75% off, because the beam is turned on during a specific “window” of the respiration cycle and turned off the remainder. Because the total treatment time for IMRT is longer than conventional delivery, further increasing the treatment time with breath-holds and gating only increases the probability of spurious intra-fraction patient motion (such as shifting unrelated to respiration). In addition breath-holds are uncomfortable, particularly for patients with compromised pulmonary capacity. With this type of motion management, the radiation can only be delivered during breath-holds which may last 10-20 s or less, depending on the patient's ability to hold their breath. The time of treatment delivery assumes even more significant role in IMRT treatments. Each 3-D conformal field can be delivered in 1-2 breath-hold cycles. However IMRT treatments involve 2-10 times as many monitor units (a measure of radiation dose delivered to a patient), and thus involve up to about 20 breath holds. Thus breath-holds during IMRT treatments not only prolong the treatment time, but also make it difficult for patients, who increasingly fatigue as treatment progresses. Hence, such respiration management strategies may not be applicable to a significant population of patients.
Gating techniques involve radiation delivery during a pre-defined window of the respiration cycle. The duty cycle is typically 25%. Thus 75% of the time the patient receives no treatment as the tumor target is out of range. In addition, tumor motion can still occur during the gating interval. If the amplitude of this motion is significant, it could adversely impact the planned dose distribution. As with breath-holds, gating methods prolong time for treatment delivery thereby increasing the chances of spurious patient motion.
Tumor-tracking methods have distinct advantages over breath-holds and gating methods by reducing treatment delay and patient discomfort. However, they are technically more challenging. In one approach, tumor-tracking adjusts the linear accelerator or its collimator (e.g., the multi-leaf collimator, MLC) to keep the moving tumor in focus. One method is to use multiple sets of CT images each associated with a specific breathing phase measured using some type of breathing sensor or a surrogate measure. Another method is to use simultaneous x-ray imaging of implanted markers under fluoroscopy and breathing monitoring using sensors or other surrogates. During delivery, the radiation starts at a pre-determined phase, at which the radiation beam is pointed at the target corresponding to this breathing phase. Patient breathing is continuously monitored and the position of the tumor is determined according to the predetermined relationship. Ideally, the beam is adjusted in real-time based on the breathing signal to track the movement of the target. However, after determining the current position of the tumor, there is some finite time delay in the displacement response of the MLC.
Furthermore, use of the MLC to follow movement reduces the capacity of the MLC to provide intensity modulation in multiple planes and increases wear on an expensive and sensitive piece of equipment. An MLC can compensate for tumor motion in two dimensions only, and the spatial resolution in one direction is limited by the width of the leaf (e.g. 0.5 cm). For an MLC, beam alignment (or control) relative to the tumor can be maintained only in the plane of treatment field. If the tumor moves out of plane, the treatment plan integrity may be compromised. Additionally, intensity-modulated radiation therapy (IMRT) and intensity modulated arc delivery (IMAT) involve significant physical movement on the part of the MLC to begin with, especially, when one considers that as many as 30% of the patients in our clinic are treated with IMRT for various disease sites. To further impose a breathing-induced motion on the MLC could exceed the physical limits of the device, such as leaf speed. Such additional motion will also lead to excessive wear and tear on the MLC and shorten its lifespan. Excessive motion of the MLC also requires frequent calibration of the MLC since individual leaves have been known to lose their calibration due to overuse
For periodic motion, such as respiratory motion, advanced prediction methods such as the use of an adaptive filter (Ozhasoglu, C. and Murphy, M J., Issues in respiratory motion compensation during external-beam radiotherapy. Int J Radiat Oncol Biol Phys vol. 52, pp 1389-1399, 2002) have been proposed. It has also been shown that the reproducibility of respiration patterns can be improved with audio visual aids and patient coaching (Vedam S S, Kini V R, Keall P J, Ramakrishnan V, Mostafavi H, Mohan R., Quantifying the predictability of diaphragm motion using an external respiratory signal. Med Phys vol. 30, pp 505-513, 2003). However, methods that involve control of patient action may not be suitable for all patients.
Based on the foregoing, there is a clear need for patient treatment delivery techniques that do not suffer all the deficiencies in prior art approaches. In particular, there is a need to track tumor motion in real time that accounts for differences between pre-treatment breathing patterns and breathing patterns during treatment. There is an independent need for techniques to compensate for tumor motion without movement of a treatment delivery device, such as an accelerator or a multi-leaf collimator (MLC).